Browsing by Subject "Methylphenidate"

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    Anti-hypotensive treatment and endothelin blockade synergistically antagonize exercise fatigue in rats under simulated high altitude.
    (PLoS One, 2014) Radiloff, Daniel; Zhao, Yulin; Boico, Alina; Blueschke, Gert; Palmer, Gregory; Fontanella, Andrew; Dewhirst, Mark; Piantadosi, Claude A; Noveck, Robert; Irwin, David; Hamilton, Karyn; Klitzman, Bruce; Schroeder, Thies
    Rapid ascent to high altitude causes illness and fatigue, and there is a demand for effective acute treatments to alleviate such effects. We hypothesized that increased oxygen delivery to the tissue using a combination of a hypertensive agent and an endothelin receptor A antagonist drugs would limit exercise-induced fatigue at simulated high altitude. Our data showed that the combination of 0.1 mg/kg ambrisentan with either 20 mg/kg ephedrine or 10 mg/kg methylphenidate significantly improved exercise duration in rats at simulated altitude of 4,267 m, whereas the individual compounds did not. In normoxic, anesthetized rats, ephedrine alone and in combination with ambrisentan increased heart rate, peripheral blood flow, carotid and pulmonary arterial pressures, breathing rate, and vastus lateralis muscle oxygenation, but under inspired hypoxia, only the combination treatment significantly enhanced muscle oxygenation. Our results suggest that sympathomimetic agents combined with endothelin-A receptor blockers offset altitude-induced fatigue in rats by synergistically increasing the delivery rate of oxygen to hypoxic muscle by concomitantly augmenting perfusion pressure and improving capillary conductance in the skeletal muscle. Our findings might therefore serve as a basis to develop an effective treatment to prevent high-altitude illness and fatigue in humans.
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    Effects of sub-chronic methylphenidate on risk-taking and sociability in zebrafish (Danio rerio).
    (Naunyn-Schmiedeberg's archives of pharmacology, 2020-08) Brenner, Rebecca G; Oliveri, Anthony N; Sinnott-Armstrong, Walter; Levin, Edward D
    Attention deficit hyperactive disorder (ADHD) is the most common psychiatric disorder in children affecting around 11% of children 4-17 years of age (CDC 2019). Children with ADHD are widely treated with stimulant medications such as methylphenidate (Ritalin®). However, there has been little research on the developmental effects of methylphenidate on risk-taking and sociability. We investigated in zebrafish the potential developmental neurobehavioral toxicity of methylphenidate on these behavioral functions. We chose zebrafish because they provide a model with extensive genetic tools for future mechanistic studies. We studied whether sub-chronic methylphenidate exposure during juvenile development causes neurobehavioral impairments in zebrafish. Methylphenidate diminished responses to environmental stimuli after both acute and sub-chronic dosing. In adult zebrafish, acute methylphenidate impaired avoidance of an approaching visual stimulus modeling a predator and decreased locomotor response to the social visual stimulus of conspecifics. Adult zebrafish dosed acutely with methylphenidate demonstrated behaviors of less retreat from threatening visual stimuli and less approach to conspecifics compared with controls. In a sub-chronic dosing paradigm during development, methylphenidate caused less robust exploration of a novel tank. In the predator avoidance paradigm, sub-chronic dosing that began at an older age (28 dpf) decreased activity levels more than sub-chronic dosing that began at earlier ages (14 dpf and 21 dpf). In the social shoaling task, sub-chronic methylphenidate attenuated reaction to the social stimulus. Acute and developmental methylphenidate exposure decreased response to environmental cues. Additional research is needed to determine critical mechanisms for these effects and to see how these results may be translatable to neurobehavioral toxicity of prescribing Ritalin® to children and adolescents.
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    Misuse of methamphetamine and prescription stimulants among youths and young adults in the community.
    (Drug and alcohol dependence, 2007-07) Wu, Li-Tzy; Pilowsky, Daniel J; Schlenger, William E; Galvin, Deborah M
    Gender differences in the prevalence and characteristics of misuse of methamphetamine (meth) and prescription stimulants were examined in a representative US sample of youths and young adults aged 16-25 (N=24,409).Stimulant misusers were categorized into three mutually exclusive subgroups: meth users only, meth and prescription stimulant users, and prescription stimulant users only (e.g., Benzedrine, Ritalin, or Dexedrine). Multinominal logistic regression analyses identified the characteristics associated with misuse of meth and prescription stimulants.About 1 in 10 youths reported any misuse of stimulants in their lifetime. Prescription stimulant misuse occurred earlier and was more frequent than meth misuse. About 47% of meth misusers also reported prescription stimulant misuse. Among misusers of meth and prescription stimulants, males were more likely than females to misuse methylphenidate (82% versus 65%) but were less likely to misuse diet pills or amphetamines (37% versus 49%). Multinominal logistic regression analyses indicated that all subgroups of lifetime stimulant misuse were associated with past year substance abuse. The characteristics of meth misusers differed slightly from prescription stimulants misusers.Multidrug use is common among stimulant misusers. Parents should be informed about the risk of prescription stimulant misuse by their youths.